title: Structural insights into functional overlapping and differentiation among myosin V motors.
abstract: Myosin V (MyoV) motors have been implicated in the intracellular transport of diverse cargoes including vesicles, organelles, RNA-protein complexes, and regulatory proteins. Here, we have solved the cargo-binding domain (CBD) structures of the three human MyoV paralogs (Va, Vb, and Vc), revealing subtle structural changes that drive functional differentiation and a novel redox mechanism controlling the CBD dimerization process, which is unique for the MyoVc subclass. Moreover, the cargo- and motor-binding sites were structurally assigned, indicating the conservation of residues involved in the recognition of adaptors for peroxisome transport and providing high resolution insights into motor domain inhibition by CBD. These results contribute to understanding the structural requirements for cargo transport, autoinhibition, and regulatory mechanisms in myosin V motors.
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil.
authors.forename: Andrey F Z
authors.initials: AFZ
authors.lastname: Nascimento
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Trindade
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil.
authors.forename: Celisa C C
authors.initials: CCC
authors.lastname: Tonoli
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil.
authors.forename: Priscila O
authors.initials: PO
authors.lastname: de Giuseppe
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil.
authors.forename: Leandro H P
authors.initials: LHP
authors.lastname: Assis
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil.
authors.forename: Rodrigo V
authors.initials: RV
authors.lastname: Honorato
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil.
authors.forename: Paulo S L
authors.initials: PSL
authors.lastname: de Oliveira
authors.affiliation: Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Pravin
authors.initials: P
authors.lastname: Mahajan
authors.affiliation: Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Burgess-Brown
authors.affiliation: Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: von Delft
authors.affiliation: Department of Cellular & Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, São Paulo 14049-900, Brazil.
authors.forename: Roy E
authors.initials: RE
authors.lastname: Larson
authors.affiliation: Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083-100, Brazil. Electronic address: mario.murakami@lnbio.cnpem.br.
authors.forename: Mario T
authors.initials: MT
authors.lastname: Murakami
mesh_terms: D001665:Binding Sites; D001693:Biological Transport, Active / Q000502:physiology; D006801:Humans; D024701:Myosin Type V / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020675:Peroxisomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D024701:Myosin Type V
keywords: Cargo-binding Domain; Cell Signaling; Crystal Structure; Intracellular Trafficking; Molecular Motors; Molecular Plasticity; Myosin; Myosin V; Redox Dimerization